Antibody-dependent cell-mediated cytotoxicity triggered by dietary antigens in cow's milk protein intolerance and coeliac disease

Abstract

Small amounts of dietary proteins pass undegraded into the circulation, an event initiating antibody production. Antibodies to dietary antigens might be beneficial by immune elimination of antigen as well as potentially disease-provoking by eliciting harmful immune effector functions, such as immune complex-mediated complement activation or antibody-dependent cell-mediated cytotoxicity (ADCC). The biological activities of antibodies are related to their characteristics, such as isotope, epitope specificity and avidity.The aim of the study was to evaluate characteristics of serum antibodies to dietary anti-gens in children with food allergy/intolerance, focussing on ADCC-mediating capacity, isotype/subclass pattern and avidity.Sera were analysed with regard to ADCC-mediating capacity, i.e. lysis of target cells (erythrocytes coated with dietary antigen) in the presence of cytotoxic effector cells (NK cells or monocytes). Serum antibody levels of IgG, IgG subclasses and IgA against b-lactoglobulin or gliadin were determined with ELISA. Affinity chromatography was used for selective depletion of IgG subclasses. Antibody avidity was estimated using a thiocyanate elution enzyme immunoassay.Sera from children with cow´s milk protein intolerance (CMPI) and gastrointestinal symptomatology showed a substantial ADCC reactivity in a b-lactoglobulin-specific system with NK cells as effectors. Coeliac children exhibited moderate ADCC reactivity of their sera, despite high levels of antibodies against b-lactoglobulin. Absorption experiments indicated that primarily IgG1 antibodies were responsible for this b-lactoglobulin-specific ADCC reactivity. Accordingly, ADCC reactivity of indi-vidual sera correlated with IgG1 anti-b-lactoglobulin antibody levels. Sera from CMPI children with gastrointestinal symptoms, most of which had a high ADCC reactivity, also had a distinctive subclass pattern of their anti-b-lactoglobulin antibodies with high relative proportions of IgG1.Sera from coeliac children had poor capacity to mediate NK cell-induced ADCC against gliadin-coated target cells. However, using monocytes as ADCC effector cells, sera from children with active coeliac disease showed a substantial ADCC-mediating capacity. Depletion of IgG1 markedly diminished the ADCC, indicating that IgG1 anti-bodies against gliadin predominantly mediate this gliadin-specific monocyte ADCC. Further, IgG1 as well as IgG3 correlated positively to ADCC reactivity.The avidity of antibodies against dietary antigens seemed to increase progressively during early childhood in healthy as well as diseased children. Active coeliac disease was connected with an accelerated avidity maturation.It is conceivable that several immune effector mechanisms may coexist and synergize in the disease process of food allergy/intolerance. The results of the present study suggest that IgG antibodies against gliadin or b-lactoglobulin, predominantly of the IgG1 iso-type, may be involved in the disease process of coeliac disease or CMPI with gastroin-testinal symptoms, via their capacity to mediate an ADCC reaction